Randomized multicenter phase II study of flavopiridol (alvocidib), cytarabine, and mitoxantrone (FLAM) versus cytarabine/daunorubicin (7+3) in newly diagnosed acute myeloid leukemia

Serial studies have demonstrated that induction therapy with FLAM [flavopiridol 50 mg/m(2) days 1-3, cytarabine 667 mg/m(2)/day continuous infusion days 6-8, and mitoxantrone 40 mg/m(2) day 9] yields complete remission rates of nearly 70% in newly diagnosed poor-risk acute myeloid leukemia. Between May 2011-July 2013, 165 newly diagnosed acute myeloid leukemia patients (18-70 years) with intermediate/adverse-risk cytogenetics were randomized 2:1 to receive FLAM or 7+3 (cytarabine 100 mg/m(2)/day continuous infusion days 1-7 and daunorubicin 90 mg/m(2) days 1-3), across 10 institutions. Some patients on 7+3 with residual leukemia on day 14 received 5+2 (cytarabine 100 mg/m(2)/day continuous infusion days 1-5 and daunorubicin 45 mg/m(2) days 1-2), whereas patients on FLAM were not retreated based on day 14 bone marrow findings. The primary objective was to compare complete remission rates between 1 cycle of FLAM and 1 cycle of 7+3. Secondary endpoints included safety, overall survival and event-free survival. FLAM led to higher complete remission rates than 7+3 alone (70% vs. 46%, p=0.003) without an increase in toxicity, and this improvement persisted after 7+3+/-5+2 (70% vs. 57%, p=0.08). There were no significant differences in overall survival and event-free survival in both arms but post-induction strategies were not standardized. These results substantiate the efficacy of FLAM induction in newly diagnosed AML. A phase 3 study is currently in development.